The Department of Psychiatry at Duke University Medical Center proposes a Clinical Research Center for the Study of Depressive Disorders in Late Life. The primary goal of the Center is to define and validate a limited number of depressives sub-types in late life that are clinically relevant and prime for further study because of recent advances in the neurosciences, nosology, epidemiology and biological approaches to therapy. Specifically, the Duke Center will screen elderly (60 + years of age) inpatients and outpatients in order to admit an average of 100 patients into the core protocol of the study each year during the first three years of the project. A series of studies have been selected to achieve the goals of the Duke Center, which include: 1) an initial screening procedure that includes both lay and clinicl interviews; 2) a study of the phenomenology of late life depression in both clinical and community populations; 3) a study of potential biological markers for depression in late life, specifically the dexamethasone suppression test, thyroid functioning, tritiated impramine binding, a study of pharmacokinetic differences which may underlie reported age related differences in tricyclic antidepressant response and a validation of the CNS significance of platelet uptake features and uptake kinetics relative to repeated tricyclic antidepressant administration; and 4) two studies of therapeutic intervention, one which assesses the response to nortriptyline compared with nortriptyline plus T3 and a second study comparing nortriptyline to pulse unilateral nondominant ECT. Four sub-types of late life depression: 1) major depressive episodes; 2) dythmymia; 3) atypical depression; and 4) adjustment disorder with depressed mood, will be specifically considered in this proposal. These disorders were chosen because they appear to have different causes, courses, outcomes and response to therapy. The recent advances in methodology and technology which are well represnted at Duke make possible a more definitive approach to reliable and valid nosological classification of depression in later years and these advances make possible the development of a center that can prove extremely useful for clinical research of etiology and assessment of treatment and outcome.